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Infectious mononucleosis. Complexities of a common syndrome.

Infectious mononucleosis is common in adolescents and young adults. Although the syndrome is most often associated with Epstein-Barr virus, several other organisms can also cause infectious mononucleosis. Diagnosis is based on clinical findings and the presence of heterophil antibodies and atypical lymphocytes. Diagnosis may be more difficult in older adults because the presenting symptoms often differ from those seen in children. Symptoms usually resolve in 2 to 3 weeks. Treatment of uncomplicated infectious mononucleosis is supportive, but corticosteroids may be beneficial for the treatment of several complications associated with Epstein-Barr virus. Physically active patients should be counseled about the risks of splenic injury.

Adolescent↗

[Asymptomatic subcapsular splenic hematoma in infectious mononucleosis (Pfeiffer disease)].

Splenic rupture in infectious mononucleosis (Pfeiffer disease, or glandular fever) is a rare but life-threatening complication. The exact mechanism of rupture of the spleen is unknown to date. A case of a spontaneous, asymptomatic, subcapsular haematoma of the spleen of an eighteen-year old female with infectious mononucleosis is presented with special reference to the echographic findings. A complete remission without any complication was obtained. The contribution of the sonographic examination and follow-up in the diagnosis of infectious mononucleosis is emphasised.

Adolescent↗

Recovery from infectious mononucleosis: a case for more than symptomatic therapy? A systematic review.

Infectious mononucleosis is usually an acute, transiently incapacitating condition, but for some sufferers it precipitates chronic illness. It is unclear which patients are at risk of a prolonged state of illness following onset of infectious mononucleosis and if there are any useful preventive measures that would facilitate recovery. The aim of this study was to review all cohort studies and intervention trials that provide information on: (a) the longitudinal course of ill health subsequent to the onset of infectious mononucleosis; (b) the relationship between psychosocial and clinical factors and recovery rate; and (c) the effect of interventions on recovery. A systematic review was conducted, based on a search of the PSYCHINFO, MEDLINE, EMBASE and CINHAL databases up to October 2001, and ISI Science and Social Sciences Citation Indices up to 22 November 2001. Eight papers were identified that gave data on illness following onset of infectious mononucleosis. The best evidence concluded that there is a distinct fatigue syndrome after infectious mononucleosis. Eight papers explored risk factors for prolonged illness following acute infectious mononucleosis. Results varied on the association of acute illness characteristics and psychological features with prolonged ill health. Poor physical functioning, namely lengthy convalescence and being less fit or active, consistently predicted chronic ill health. Three trials reported on interventions that aimed to shorten the time taken to resolve symptoms after uncomplicated infectious mononucleosis. None of the drug trials found any evidence that drug therapy shortens recovery time. The trial that compared the effect of activity with imposed bed rest, found that those patients allowed out of bed as soon as they felt able reported a quicker recovery. More information is needed on the course of ill health subsequent to the onset of infectious mononucleosis. Certain risk factors associated with delay may be amenable to a simple intervention in primary care.

Chronic Disease↗

Abrogation of cell-mediated immunity by a serum blocking factor isolated from patients with infectious mononucleosis.

Lymphocytes from 80% of patients with infectious mononucleosis in this study failed to produce macrophage migration-inhibition factor in response to partially purified early antigen of Epstein-Barr virus or to tetanus toxoid, whereas lymphocytes from normal subjects did produce this lymphokine. Subsequent analysis of serum from the patients with infectious mononucleosis revealed a serum factor that completely abrogated antigen-specific inhibition of migration by human leukocytes as well as lymphocyte blastogenesis. The serum blocking factor was present in sera from 11 (73%) of 15 patients with infectious mononucleos but only in sera from two (13%) of 15 normal subjects. Samples of serum from five of the patients with infectious mononucleosis and five normal subjects were fractionated with use of Sephadex G-200 gel filtration, and the eluants were assayed for several substances known to inhibit cell-mediated immunity. Serum blocking factor activity could be demonstrated only in fractionated sera from patients with infectious mononucleosis. The serum blocking factor is postulated to be either a soluble immune complex or some as yet unidentified immunoregulatory globulin contained in the IgG fraction of human serum.

Antigen-Antibody Complex↗

Multiple sclerosis after infectious mononucleosis: record linkage study.

OBJECTIVE: To ascertain if infectious mononucleosis is a risk factor for the development of multiple sclerosis (MS); and, if it is, whether its effect is close to or remote in time from the onset of MS. DESIGN: Analysis of database of linked abstracts of records of hospital admission and death. SETTING: Health region in central southern England. MAIN OUTCOME MEASURE: Ratio of rate of MS in a cohort of people admitted to hospital with infectious mononucleosis to the rate in a comparison cohort. RESULTS: Considering all time intervals from admission with infection to admission with MS, there was a non-significant increase of risk of MS in the infectious mononucleosis cohort (rate ratio 2.17, 95% confidence intervals 0.79 to 4.77). At the interval of 10 years or more, there was a significant increase in risk of MS (rate ratio 4.01, 1.48 to 8.93). The mean time from infectious mononucleosis to first admission with MS was 14 years. CONCLUSION: This study adds support to the evidence that Epstein-Barr virus, the cause of infectious mononucleosis, is associated with MS. Its role is probably as an initiator of the disease process of MS, or as a contributor to its early development, rather than as an activator of latent, existing disease.

Adolescent↗

Cervical abscess: a life-threatening complication of infectious mononucleosis.

The former view of infectious mononucleosis as an invariably benign disease has been modified in recent years by reports of life-threatening complications. A case is presented of a deep cervical abscess complicating infectious mononucleosis which came close to a fatal conclusion. The implications for the management of the illness are discussed in the light of this rare event, no exactly similar instance of which has been recorded.

Abscess↗

[Acute obstructive nasal syndrome as expression of infectious mononucleosis. A case report].

The infectious mononucleosis (IM) is a disease which mainly affects people between 15 and 24 years old. We present a case of a men, of 42 years, who has an infectious mononucleosis localized in the nasopharynx area, as its first and unique feature. This patient was admitted at hospital for an urgent treatment. We refer the clinical symptoms, diagnose, main complications and treatment of the condition.

Acute Disease↗

Characteristic T cell dysfunction in patients with chronic active Epstein-Barr virus infection (chronic infectious mononucleosis).

We evaluated immune functions in 16 patients with chronic active Epstein-Barr virus (EBV) infection (chronic infectious mononucleosis). Chronic infectious mononucleosis is an illness characterized primarily by chronic and occasionally disabling fatigue and other constitutional complaints, only sometimes beginning with an episode of acute infectious mononucleosis, and associated with an abnormal pattern of serum antibodies to EBV. In these patients, the frequency of circulating EBV-infected B cells that manifested spontaneous outgrowth in vitro was comparable to that found in EBV-seropositive normals, and the levels of EBV-specific suppressor activity were also normal. Upon stimulation with polyclonal activators, unseparated cells from these patients produced a relatively normal number of immunoglobulin-secreting cells. However, when purified T cells from these patients were mixed with normal mononuclear cells in co-culture, immunoglobulin production was strikingly suppressed. The degree of this T cell suppression correlated directly with the abnormally elevated titer of antibody to the early antigens of EBV. Interestingly, during normal convalescence from acute EBV-induced infectious mononucleosis a period is also seen during which T cells suppress the response of allogeneic but not autologous cells. Thus, from an immunologic viewpoint, patients with chronic active EBV infection appear "frozen" in a state typically found only briefly during the convalescence from acute EBV infection.

Adolescent↗

Quantitation of a slide test (Monotest) for infectious mononucleosis.

A slide test for infectious mononucleosis using formalinized horse erythrocytes (Monotest(2)) was quantitated and compared with standard differential heterophile (Davidsohn) titres performed on the same specimens. The Monotest titre parallels the standard presumptive heterophile (antisheep cell) titre in the degree of elevation, with a ratio of Monotest to heterophile titre of approximately 1 to 56. The simplicity of the quantitative slide test recommends it as a routine test for infectious mononucleosis.

Animals↗

[Bilateral lid swelling during infectious mononucleosis (Hoagland-sign)].

BACKGROUND: Infectious mononucleosis ("kissing disease") is an infection caused by Epstein-Barr-Virus (EBV, human herpes virus 4). METHODS: We present the case of an 18-year old female patient with dacryoadenitis and sub-febrile temperatures followed by a distinct feeling of sickness. RESULTS: Laboratory results revealed a Leukocytosis of 16.3 G/I with explicit elevation of hepatic parameters. The ultrasound scan of the orbital region showed a bilateral, echo-reduced, compressible lesion in the area of the lachrymal gland. The abdomen-ultrasound scan revealed a splenomegaly and the size of the liver was within normal limits. Serology was positive for EBV-VCA-IgG, EBV-EA-IgG and EBV-VCA-IgM. CONCLUSIONS: A dacryoadenitis can be the presenting symptom of an infectious mononucleosis.

Adolescent↗

[Hematologic complications in infectious mononucleosis].

In three patients with infectious mononucleosis the disease was severely complicated by, respectively, aplastic anemia, consumptive thrombocytopenia and hemolytic anemia with acute renal failure. In contrast to the regularly recurring basic signs and symptoms of the illness, serious complications occur in less than 1% of all patients. Changes in the immunologic system seem to play an important role in hematologic and other complications, as well as in the occasionally fatal Epstein-Barr virus infection. Pathophysiological, and particularly immunologic mechanisms, and possible therapy are discussed with reference to case reports of patients with similar clinical courses and the literature on infectious mononucleosis.

Acute Kidney Injury↗

Atypical clonal T-cell proliferation in infectious mononucleosis.

An atypical case of infectious mononucleosis characterized by fever, acute tonsillitis, and bilateral cervical adenopathy is reported in a previously healthy young man. Although serology was positive for the Epstein-Barr virus, the patient did not display peripheral blood lymphocytosis or atypical, reactive lymphocytes. The patient's tonsilar tissue revealed an expanded T-zone of diffuse, monomorphous lymphocytes suggestive of lymphoma. Immunophenotypic analysis of the tonsilar tissue demonstrated more than 90% expression of pan-T markers, while pan-B markers were positive in 5-10% of the interfollicular T-zone cells and in 90% of germinal centre cells. In situ hybridization with a probe specific for EBER1 demonstrated positive staining in approximately 1% of the interfollicular tonsilar lymphocytes. Finally, Southern blot analysis of tonsilar tissue demonstrated a clonal rearrangement of the T-cell receptor gene. The patient recovered from his infection and remains in good health years after presenting with his illness. This case illustrates that T-cell clonality must be evaluated with caution in the setting of a viral infection and can occur in association with benign, self-limited infectious mononucleosis.

Adult↗

Paul-Bunnell antigen and a possible mechanism of formation of heterophile antibodies in patients with infectious mononucleosis.

Sera of patients with infectious mononucleosis contain heterophile anti-Paul- Bunnell (PB) antibodies to erythrocytes of numerous mammalian species. Evidence is presented that the corresponding antigen of bovine erythrocytes is not, as previously described, a single molecule, but a series of glycoproteins with glycans terminated with N-glycolylneuraminic acid (Neu5Gc). The latter compound should be an important part of the PB epitope because, in agreement with the results of others, we found that desialylation of the PB antigen abolishes almost completely its activity. We examined three different preparations of GM3 ganglioside for their capacity to bind anti-PB and found that only GM3 from horse erythrocytes containing Neu5Gc exhibited a low although ELISA measurable PB activity. The other two GM3 preparations, from bovine milk and dog erythrocytes, containing N-acetylneuraminic acid (Neu5Ac) bound little if any anti-PB antibodies. This finding confirms a previous report that human erythrocyte Neu5Ac containing sialoglycoprotein with similar O-linked glycans as the PB-antigen of bovine erythrocytes exhibits only very low PB activity (Patarca & Fletcher, 1995, Crit Rev Oncogen., 6: 305). In conclusion, we present a hypothesis that anti-PB antibodies in patients with infectious mononucleosis are formed against infection-induced cell membrane glycoconjugates containing highly immunogenic Neu5Gc.

Animals↗

Cephalexin rash in infectious mononucleosis.

The ampicillin rash occurring in cases of infectious mononucleosis is well documented. Similar phenomena have also been observed with other antibiotics. The case of a patient with infectious mononucleosis treated with cephalexin who later showed a rash is presented and the previous literature is reviewed. The rash seen in this patient, who was treated with cephalexin, may be similar to the rash seen with ampicillin treatment of patients with infectious mononucleosis. The mechanism by which these eruptions occur is not completely understood, although there are many interesting theories. Perhaps rashes during infectious mononucleosis in association with other antibiotics are actually more common, but just not recognized. A heightened awareness of this possibility may therefore lead to recognition of more cases and further understanding of this entity.

Adult↗

Hematopoietic and lymphatic cancers in relatives of patients with infectious mononucleosis.

BACKGROUND: Young adults with a history of Epstein-Barr virus (EBV)-related infectious mononucleosis have an increased risk for Hodgkin's lymphoma. EBV is detected in Hodgkin's lymphoma Reed-Sternberg cells from some patients, but in young adult patients, it is detected at a relatively low frequency in these cells. Hodgkin's lymphoma and infectious mononucleosis are both associated with high social class, and unknown confounding factors that are also associated with socioeconomic status might explain or contribute to the apparent association between these diseases. To indirectly assess the importance of socioeconomic status on the association between these diseases, we determined the risk for hematopoietic and lymphatic cancers in first-degree relatives of patients with confirmed EBV-related infectious mononucleosis. METHODS: We identified parents, siblings, and offspring of 17,045 persons with serologically confirmed EBV-related infectious mononucleosis. Subjects in these cohorts were linked with the population-based Danish Cancer Register to identify those developing hematopoietic/lymphatic cancers after the index patient was diagnosed with infectious mononucleosis. The relative risk for cancer in the infectious mononucleosis family members was expressed as standardized incidence ratios (SIRs; i.e., the ratio between the number of cancers observed and the number of cancers expected, obtained from age-specific, sex-specific, and period-specific incidence rates). RESULTS: We identified 8052 parents, 5264 siblings, and 28,605 offspring of patients with EBV-related infectious mononucleosis who were followed for a total of 892,213 person-years at risk. The risk for Hodgkin's lymphoma was unaltered in the combined group of first-degree relatives of these patients (SIR = 0.99; 95% confidence interval [95% CI] = 0.62 to 1.59; number of cases [n] = 17), in the group of parents (SIR = 0.83; 95% CI = 0.31 to 2.22; n = 4), in the group of siblings (SIR = 0.96; 95% CI = 0.31 to 2.97; n = 3), and in the group of offspring (SIR = 1.08; 95% CI = 0.58 to 2.02; n = 10). CONCLUSION: The unremarkable risk for Hodgkin's lymphoma in family members of patients with EBV-related infectious mononucleosis indicates that socioeconomic confounding is an unlikely explanation for the association between EBV-related infectious mononucleosis and Hodgkin's lymphoma.

Adult↗

Pseudoappendicitis preceding infectious mononucleosis.

In patients with infectious mononucleosis, abdominal pain is usually attributed to visceral enlargement. A teenage girl with symptoms of appendicitis was found at laparotomy to have mesenteric adenitis. Postoperatively, she developed classic features of Epstein-Barr virus (EBV)-induced mononucleosis. The lymphoproliferation characteristic of EBV infection can cause severe localized abdominal pain that predates the onset of mononucleosis.

Abdomen, Acute↗

Splenic injury: nonoperative management in three patients with infectious mononucleosis.

Three patients with infectious mononucleosis and splenic injury were managed nonoperatively. Mechanisms of injury included significant left upper quadrant trauma during a football game in a 17-year-old boy, a minor fall in a 16-year-old girl, and no apparent trauma in the remaining patient, a 28-year-old man. All had significant abdominal pain and two were hypotensive upon admission. All had computerized tomographic scan documentation of splenic enlargement, significant injury, and free peritoneal blood. Paracentesis was not performed. Only the first patient received transfused blood. The hospitalization period ranged from nine to 14 days. Gradual and finally complete healing (return to normal size) was documented in all three patients. Follow-up is 66, 14, and 10 months. Although clearly controversial and not free from danger, successful nonoperative management of the injured enlarged spleen in select patients with mononucleosis is possible in an appropriate setting.

Adolescent↗

Gross hematuria as a manifestation of infectious mononucleosis.

Gross hematuria is an uncommon manifestation of infectious mononucleosis. This report describes a 19-year-old male with infectious mononucleosis who developed gross hematuria. Infectious mononucleosis should be considered in the differential diagnosis of adolescents with hematuria.

Adult↗